Hydrophilic crosslinked polymer

ABSTRACT

The present invention relates to a hydrophilic crosslinked polymer, preferably in the form of porous particles, and to the preparation and use thereof. The polymer according to the invention is produced by polymerisation from chain-forming hydrophilic vinyl ethers and crosslinking, preferably heterocyclic divinyl ethers.

This application claims the benefit of the filing date of InternationalApplication No.: PCT/EP2006/005296 filed Jun. 2, 2006 and isincorporated by reference herein.

The present invention relates to a hydrophilic crosslinked polymer,preferably in the form of porous particles, and to the preparation anduse thereof. The polymer according to the invention is produced bypolymerisation from chain-forming hydrophilic vinyl ethers andcrosslinking N,N′-divinyl compounds, preferably heterocyclicN,N′-divinyl compounds.

Hydrophilic, crosslinked, polymeric support materials are frequentlyemployed in areas such as chromatography, solid-phase synthesis orcatalysis. In particular for use as support material in chromatography,polymers of this type should have the following properties:

-   -   the materials should be sufficiently hydrophilic that, in        particular, use in biochromatography is possible    -   it should be possible for the materials to be modified, if        required, by means of separation effectors in order that their        separation properties can be matched to the particular        separation problem    -   the polymer must be sufficiently stable to hydrolysis    -   in particular for applications in the area of high-pressure        liquid chromatography, the material must have adequate        pressure/flow stability    -   the materials should have adequate pore sizes

In addition, it should be possible to prepare polymers of this type inas simple and reproducible a manner as possible.

WO 03/104294 discloses polyvinyl ethers, in particular for use insolid-phase synthesis. The polymers disclosed usually exhibit verystrong swelling behaviour.

DE 37 14 276 and DE 3344912 disclose crosslinked polymers based on vinylacetates. In order to produce a hydrophilic polymer, the acetate groupshave to be saponified subsequently.

WO 9513861 discloses polyvinyl ethers for separation purposes which areprepared by cationic polymerisation. The cationic polymerisationdescribed must be carried out in combination with complexprotecting-group chemistry.

EP 0 266 503 discloses crosslinked polymers which are prepared by meansof suspension polymerisation from monomers containing epoxide groups.The resultant polymers containing epoxide groups can then be used forthe immobilisation of biologically active substances.

EP 0 482 339 discloses a copolymer based on allyl monomers. Inparticular, the copolymer based on EP 0 482 339 comprising1,2,-dihydroxy-3-allyloxypropane and N,N′-methylenebisacrylamide,commercially available under the name FractoPrep® (Merck KGaA, Germany),exhibits good properties for biochromatography with respect tohydrophilicity, stability to hydrolysis and pressure/flow stability.However, the disadvantage of this material is the complex preparationprocess by means of inverse suspension polymerisation.

The object of the present invention was therefore to provide ahydrophilic polymeric support material which meets the above-mentionedrequirements with respect to porosity, hydrophilicity, stability tohydrolysis and pressure/flow stability and in addition is simple toprepare.

It has been found that copolymerisation of hydrophilically substitutedalkyl vinyl ethers using crosslinking, preferably heterocyclicN,N′-divinyl compounds enables the preparation of hydrophilic polymershaving good properties, in particular for biochromatography. Thepolymers are preferably prepared by means of suspension polymerisation.

The present invention therefore relates to a hydrophilic crosslinkedpolymer based on a copolymer at least comprising

-   a) at least one hydrophilically substituted alkyl vinyl ether of the    formula I

where R1, R2, R3, independently of one another, can be H or C1 to C6alkyl, preferably H or —CH₃,

-   and R4 is a radical which carries at least one hydroxyl group-   and-   b)-   at least one crosslinking agent conforming to formula II and/or III    and/or IV with

where X is a divalent alkyl radical having 2 to 5 C atoms, preferably 2or 3 C atoms, in which one or more methylene groups which are notadjacent and are not located in the direct vicinity of N may be replacedby O, C═O, S, S═O, SO₂, NH, NOH or N and one or more H atoms of themethylene groups may be substituted, independently of one another, byhydroxyl groups, C1-C6-alkyl, halogen, NH₂, C5-C10-aryl,NH—(C1-C8)-alkyl, N—(C1-C8)-alkyl₂, C1-C6-alkoxy or C1-C6-alkyl-OH, and

where Y1 and Y2 in formula III and IV are, independently of one another,

-   C1 to C10 alkyl or cycloalkyl, where one or more non-adjacent    methylene groups or methylene groups which are not located in the    direct vicinity of N may be replaced by O, C═O, S, S═O, SO₂, NH, NOH    or N and one or more H of the methylene groups may be substituted,    independently of one another, by hydroxyl groups, C1-C6-alkyl,    halogen, NH₂, C5-C10-aryl, NH(C1-C8)alkyl, N(C1-C8)alkyl₂,    C1-C6-alkoxy or C1-C6-alkyl-OH,-   or C6 to C18 aryl, where one or more H in the aryl system may be    substituted, independently of one another, by hydroxyl groups,    C1-C6-alkyl, halogen, NH₂, NH(C1-C8)alkyl, N(C1-C8)alkyl₂,    C1-C6-alkoxy or C1-C6-alkyl-OH and-   A is a divalent alkyl radical having 2 to 5 C atoms, preferably 2 or    3 C atoms, in which one or more non-adjacent methylene groups or    methylene groups which are not located in the direct vicinity of N    may be replaced by O, C═O, S, S═O, SO₂, NH, NOH or N and one or more    H of the methylene groups may be substituted, independently of one    another, by hydroxyl groups, C1-C6-alkyl, halogen, NH₂, C5-C10-aryl,    NH(C1-C8)alkyl, N(C1-C8)alkyl₂, C1-C6-alkoxy or C1-C6-alkyl-OH.-   R4 in formula I is typically an alkyl radical, a cycloaliphatic    radical or an aryl radical which carries at least one hydroxyl    group.

In a preferred embodiment, R4 in formula I is

-   a straight-chain or branched C1 to C10 alkyl radical, in which one    or more non-adjacent methylene groups may be replaced by O, C═O, S,    S═O, SO₂, NH, NOH, N and/or in which one or more H atoms may be    substituted, independently of one another, by C1-C6-alkyl,    C5-C10-aryl, halogen, NH₂, NH(C1-C8)alkyl, N(C1-C8)alkyl₂,    C1-C6-alkoxy or C1-C6-alkyl-OH and in which at least one OH group is    present either on the C1 to C10 alkyl radical or on a substituent,-   or a cycloaliphatic radical, typically having 5 to 10 C atoms, in    which one or more non-adjacent methylene groups may be replaced by    O, C═O, S, S═O, SO₂, NH, NOH, N and/or in which one or more H atoms    of the cycloaliphatic radical may be substituted, independently of    one another, by C1-C6-alkyl, C5-C10-aryl, halogen, NH₂,    NH(C1-C8)alkyl, N(C1-C8)alkyl₂, C1-C6-alkoxy or C1-C6-alkyl-OH,    where at least one OH group is present either on the cycloaliphatic    ring or on a side chain or substituent, or a-   C6 to C18 aryl radical, where one or more H atoms in the aryl    radical may be substituted, independently of one another, by    hydroxyl groups, C1-C6-alkyl, C5-C10-aryl, halogen, NH₂,    NH(C1-C8)alkyl, N(C1-C8)alkyl₂, C1-C6-alkoxy or C1-C6-alkyl-OH,    where at least one OH group is present either on the aryl radical or    on a side chain or substituent, or a-   C5 to C18 heteroaryl radical, where one or more H atoms in the    heteroaryl radical may be substituted, independently of one another,    by hydroxyl groups, C1-C6-alkyl, C5-C10-aryl, halogen, NH₂,    NH(C1-C8)alkyl, N(C1-C8)alkyl₂, C1-C6-alkoxy or C1-C6-alkyl-OH,    where at least one OH group is present either on the heteroaryl    radical or on a side chain or substituent.

In a particularly preferred embodiment, R4 in formula I is

-   a straight-chain or branched C1 to C10 alkyl radical, in which one    or more non-adjacent methylene groups may be replaced by O, S, SO₂    or NH and/or in which one or more H atoms may be substituted,    independently of one another, by C1-C6-alkyl, C5-C10-aryl,    C1-C6-alkoxy or C1-C6-alkyl-OH and in which at least one OH group is    present either on the C1 to C10 alkyl radical or on a substituent,-   or a cycloaliphatic radical, typically having 5 to 10 C atoms, in    which one or more non-adjacent methylene groups may be replaced by    O, S, SO₂ or NH and/or in which one or more H atoms of the    cycloaliphatic radical may be substituted, independently of one    another, by C1-C6-alkyl, C5-C10-aryl, C1-C6-alkoxy or    C1-C6-alkyl-OH, where at least one OH group is present either on the    cycloaliphatic ring or on a side chain or substituent, or a-   C6 to C14 aryl radical, where one or more H atoms in the aryl    radical may be substituted, independently of one another, by    hydroxyl groups, C1-C6-alkyl, C5-C10-aryl, C1-C6-alkoxy or    C1-C6-alkyl-OH, where at least one OH group is present either on the    aryl radical or on a side chain or substituent, or a-   C6 to C14 heteroaryl radical, in which at least one N atom is    present as heteroatom and where one or more H atoms in the    heteroaryl radical may be substituted, independently of one another,    by hydroxyl groups, C1-C6-alkyl, C5-C10-aryl, C1-C6-alkoxy or    C1-C6-alkyl-OH, where at least one OH group is present either on the    heteroaryl radical or on a side chain or substituent.

In a preferred embodiment, the hydrophilically substituted alkyl vinylether employed is a compound of the formula I in which R4 is a radicalwhich carries a hydroxyl group.

In a particularly preferred embodiment, the hydrophilically substitutedalkyl vinyl ether employed is 1,2-ethanediol monovinyl ether,1,3-propanediol monovinyl ether, 1,4-butanediol monovinyl ether,1,5-pentanediol monovinyl ether, 1,6-hexanediol monovinyl ether ordiethylene glycol monovinyl ether and the cycloaliphatic vinyl etheremployed is cyclohexanedimethanol monovinyl ether.

In a further preferred embodiment, the crosslinking agent employed isdivinylethyleneurea (1,3-divinylimidazolin-2-one) ordivinylpropyleneurea (1,3-divinyltetrahydropyrimidin-2-one).

In another preferred embodiment, the polymer is porous having pore sizesbetween 2 and 200 nm.

In another embodiment, the polymer is in the form of particles having adiameter between 3 and 300 μm.

In another embodiment, the polymer has been derivatised by means ofseparation effectors.

In a preferred embodiment, the polymer has been derivatised by means ofstructures which have been attached to the polymer by graftpolymerisation.

In a preferred embodiment, the polymer has been derivatised by means ofstructures which have been attached to the polymer by graftpolymerisation with cerium(IV) catalysis.

In a particularly preferred embodiment, the structures are copolymerswhich have been produced from two or more different monomers.

The present invention also relates to a process for the preparation ofpolymers, characterised in that at least one hydrophilically substitutedalkyl vinyl ether of the formula I and at least one crosslinking agentconforming to formula II and/or III and/or IV are copolymerised, with

where R1, R2, R3, independently of one another, can be H or C1 to C6alkyl, preferably H or —CH₃,and R4 is a radical which carries at least one hydroxyl group and

where X is a divalent alkyl radical having 2 to 5 C atoms, preferably 2or 3 C atoms, in which one or more methylene groups which are notadjacent and are not located in the direct vicinity of N may be replacedby O, C═O, S, S═O, SO₂, NH, NOH or N and one or more H atoms of themethylene groups may be substituted, independently of one another, byhydroxyl groups, C1-C6-alkyl, halogen, NH₂, C5-C10-aryl, NH—C1-C8-alkyl,N—C1-C8-alkyl₂, C1-C6-alkoxy or C1-C6-alkyl-OH, and

where Y1 and Y2 in formula III and IV are, independently of one another,

-   C1 to C10 alkyl or cycloalkyl, where one or more non-adjacent    methylene groups or methylene groups which are not located in the    direct vicinity of N may be replaced by O, C═O, S, S═O, SO₂, NH, NOH    or N and one or more H of the methylene groups may be substituted,    independently of one another, by hydroxyl groups, C1-C6-alkyl,    halogen, NH₂, C5-C10-aryl, NH(C1-C8)alkyl, N(C1-C8)alkyl₂,    C1-C6-alkoxy or C1-C6-alkyl-OH,-   or C6 to C18 aryl, where one or more H in the aryl system may be    substituted, independently of one another, by hydroxyl groups,    C1-C6-alkyl, halogen, NH₂, NH(C1-C8)alkyl, N(C1-C8)alkyl₂,    C1-C6-alkoxy or C1-C6-alkyl-OH and-   A is a divalent alkyl radical having 2 to 5 C atoms, preferably 2 or    3 C atoms, in which one or more non-adjacent methylene groups or    methylene groups which are not located in the direct vicinity of N    may be replaced by O, C═O, S, S═O, SO₂, NH, NOH or N and one or more    H of the methylene groups may be substituted, independently of one    another, by hydroxyl groups, C1-C6-alkyl, halogen, NH₂, C5-C10-aryl,    NH(C1-C8)alkyl, N(C1-C8)alkyl₂, C1-C6-alkoxy or C1-C6-alkyl-OH.

In a preferred embodiment, R4 in formula I is

-   a straight-chain or branched C1 to C10 alkyl radical, in which one    or more non-adjacent methylene groups may be replaced by O, C═O, S,    S═O, SO₂, NH, NOH, N and/or in which one or more H atoms may be    substituted, independently of one another, by C1-C6-alkyl,    C5-C10-aryl, halogen, NH₂, NH(C1-C8)alkyl, N(C1-C8)alkyl₂,    C1-C6-alkoxy or C1-C6-alkyl-OH and in which at least one OH group is    present either on the C1 to C10 alkyl radical or on a substituent,-   or a cycloaliphatic radical, typically having 5 to 10 C atoms, in    which one or more non-adjacent methylene groups may be replaced by    O, C═O, S, S═O, SO₂, NH, NOH, N and/or in which one or more H atoms    of the cycloaliphatic radical may be substituted, independently of    one another, by C1-C6-alkyl, C5-C10-aryl, halogen, NH₂,    NH(C1-C8)alkyl, N(C1-C8)alkyl₂, C1-C6-alkoxy or C1-C6-alkyl-OH,    where at least one OH group is present either on the cycloaliphatic    ring or on a side chain or substituent, or a C6 to C18 aryl radical,    where one or more H atoms in the aryl radical may be substituted,    independently of one another, by hydroxyl groups, C1-C6-alkyl,    C5-C10-aryl, halogen, NH₂, NH(C1-C8)alkyl, N(C1-C8)alkyl₂,    C1-C6-alkoxy or C1-C6-alkyl-OH, where at least one OH group is    present either on the aryl radical or on a side chain or    substituent, or a-   C5 to C18 heteroaryl radical, where one or more H atoms in the    heteroaryl radical may be substituted, independently of one another,    by hydroxyl groups, C1-C6-alkyl, C5-C10-aryl, halogen, NH₂,    NH(C1-C8)alkyl, N(C1-C8)alkyl₂, C1-C6-alkoxy or C1-C6-alkyl-OH,    where at least one OH group is present either on the heteroaryl    radical or on a side chain or substituent.

In a preferred embodiment, a free-radical suspension polymerisation iscarried out.

In a particularly preferred embodiment, a free-radical suspensionpolymerisation is carried out in water as suspension medium in thepresence of at least one suspension stabiliser and optional furtheradditives, preferably inorganic salts and interface-active compounds.

In an embodiment, the temperature during the polymerisation is between40 and 100° C.

In a preferred embodiment, hydrophilically substituted alkyl vinylethers and crosslinking agents are employed in a weight ratio between10:90 and 80:20.

In a preferred embodiment, the polymerisation is carried out withaddition of one or more porogens.

The present invention also relates to a chromatography column,capillary, cartridge, stirred reactor or reactor containing a polymeraccording to the invention as sorbent or support material.

The present invention also relates to the use of a hydrophiliccrosslinked polymer according to the invention as sorbent inchromatography, as support material for the immobilisation ofbiologically or catalytically active substances or as support materialfor a solid-phase synthesis.

The present invention also relates to polymers obtainable by the processaccording to the invention.

Further combinations and preferred embodiments are disclosed in thepatent claims.

FIG. 1 shows the retention behaviour of the polymer according to theinvention on application of proteins. Further details are given inExample 2.

FIG. 2 shows the experimentally determined distribution coefficient Kdof dextrans having different molecular weights. Further details aregiven in Example 3.

FIG. 3 shows the storage stability of a polymer according to theinvention in dilute sodium hydroxide solution. Further details are givenin Example 4.

FIG. 4 shows the separation of a protein mixture on a polymer accordingto the invention provided with cationic separation effectors. Furtherdetails are given in Example 5.

FIG. 5 shows the pressure/flow behaviour of the polymer according to theinvention in a chromatography column.

In accordance with the invention, the term “cycloaliphatic radical”denotes a saturated hydrocarbon radical in which all or at least some ofthe hydrocarbon units are a constituent of a cyclic structure.

In accordance with the invention, N(C1-C8)alkyl₂ denotes a nitrogenwhich is substituted by at least two alkyl radicals. The two alkylradicals here may have, independently of one another, 1 to 8 C atoms instraight-chain or branched form.

In accordance with the invention, a heteroaryl radical is an at leastpartially aromatic radical which differs from an aryl radical in thatone or more non-adjacent C atoms have been replaced by N, S or O. It isclear to the person skilled in the art that, owing to the valences, theheteroatoms may optionally be substituted by, for example, H,C1-C6-alkyl or C1-C6-alkyl-OH.

The polymer according to the invention is a hydrophilic, crosslinkedpolymer based on a copolymer at least comprising

-   a) at least one hydrophilically substituted alkyl vinyl ether of the    formula I

where the radicals R1, R2, R3 and R4 have the above-mentioned meanings,and

-   b)-   at least one crosslinking agent conforming to formula II and/or III    and/or IV

where the substituents X, A, Y1 and Y2 have the above-mentionedmeanings.

This means the polymer is formed by copolymerisation of at least onecompound from the group of the hydrophilically substituted alkyl vinylethers of the formula I and at least one compound from the group of thecrosslinking agents of the formula II and/or III and/or IV. Preferably,only one compound from the group of the hydrophilically substitutedalkyl vinyl ethers of the formula I and one compound from the group ofthe crosslinking agents of the formula II, III or IV is employed.However, it is also possible to employ one or more compounds from thegroup of the hydrophilically substituted alkyl vinyl ethers of theformula I and/or one or more compounds from the group of thecrosslinking agents of the formula II and/or III and/or IV. Furthermore,further polymerisable compounds which are copolymerised into the polymerbackbone can be added to the polymerisation mixture. These are typicallycompounds having at least one polymerisable double bond. Preferably,only one compound from the group of the hydrophilically substitutedalkyl vinyl ethers of the formula I and one compound from the group ofthe crosslinking agents of the formula II, III or IV is employed.

In a preferred embodiment, the hydrophilically substituted alkyl vinylether employed is a compound of the formula I in which R4 is a radicalwhich carries a hydroxyl group.

In a preferred embodiment, the hydrophilically substituted alkyl vinylether employed is 1,2-ethanediol monovinyl ether, 1,3-propanediolmonovinyl ether, 1,4-butanediol monovinyl ether, 1,5-pentanediolmonovinyl ether, 1,6-hexanediol monovinyl ether or diethylene glycolmonovinyl ether and the cycloaliphatic vinyl ether employed iscyclohexanedimethanol monovinyl ether, particularly preferably1,4-butanediol monovinyl ether, 1,5-pentanediol monovinyl ether,diethylene glycol monovinyl ether or cyclo-hexanedimethanol monovinylether.

The crosslinking agents employed are preferably compounds of the formulaII. Preference is given to the use of divinylpropyleneurea(1,3-divinyl-tetrahydropyrimidin-2-one) or particularly preferablydivinylethyleneurea (1,3-divinylimidazolin-2-one).

The proportion of the hydrophilically substituted alkyl vinyl etherswith respect to the weight of the polymer is typically between 1% (byweight) and 90% (by weight) or a maximum proportion by weight of thealkyl vinyl ether which corresponds to a molar ratio of 2:1, based on abifunctional crosslinking agent, if the alkyl vinyl ether does nothomopolymerise. The proportion of the hydrophilically substituted alkylvinyl ethers is preferably between 10 and 80% (% by weight),particularly preferably between 35 and 60%. Accordingly, the proportionof the crosslinking agent is between 10 and 99 (% by weight), preferablybetween 20 and 90%, particularly preferably between 40 and 65%.

The process-engineering design of the copolymerisation of unsaturatedcompounds is known to the person skilled in the art. To this end, afree-radical polymerisation is carried out. A suspension polymerisationinitiated by free radicals, also known as bead polymerisation, ispreferably carried out. Descriptions of the way in which apolymerisation of this type is carried out are given, for example, in EP1179732 A2 (general description page 4, lines 18 to 26, and page 5, line3, to page 6, line 9, and, in particular, Example 1) or in EP 0006199 B1(general description page 3, line 19, to page 4, line 13, and, inparticular, Example 1). Depending on the dissolution behaviour of themonomers, an oil-in-water suspension polymerisation (normal-phasepolymerisation) is carried out in a particularly simple procedure in thecase of water-insoluble or sparingly water-soluble monomers, which arealso known as oil. In the case of water-soluble monomers, by contrast,the latter are dissolved in water and suspended and polymerised in awater-immiscible or only sparingly water-miscible organic solvent(inverse polymerisation).

It has been found that, in particular in the case of the use ofdivinylethyleneurea or divinylpropyleneurea in combination with thepreferred hydrophilically substituted alkyl vinyl ethers, such as1,4-butanediol monovinyl ether, 1,5-pentanediol monovinyl ether,diethylene glycol monovinyl ether or cyclohexanedimethanol monovinylether, a (normal-phase) suspension polymerisation can be carried out.This offers the advantage of a very simple preparation process for thepolymers according to the invention since the hydrophilic polymer isobtained in a single reaction step without having to carry out thecomplex inverse suspension polymerisation. A further major advantage ofthe hydrophilically substituted alkyl vinyl ethers employed inaccordance with the invention is that a subsequent hydrolysis step doesnot have to be carried out in order to produce a hydrophilic polymer.Instead, the use of the hydroxyl-containing vinyl ethers as startingmaterials results in the direct formation of a hydroxyl-containingpolymer.

The suspension polymerisation is carried out in a known manner.

The suspension medium used in the normal-phase suspension polymerisationis typically water.

One or more stabilisers and/or one or more interface-active compoundscan, as is known, be added to the suspension medium.

Stabilisers which can be employed are a multiplicity of water-solublemacromolecular compounds or also finely divided inorganic compounds.

Examples of macromolecular stabilisers are polyvinylpyrrolidone,polyacrylates, polycarboxylates, polyacrylamide, polyvinyl alcohol,hydroxyalkylcellulose, methylcellulose or polyethylene glycols.Preference is given to the use of polyvinyl alcohols.

Inorganic compounds which can be employed as stabilisers are, forexample, calcium phosphate or magnesium hydroxide.

Salts, ionic liquids or buffer substances, such as, for example, Na₂HPO₄and NaH₂PO₄, can furthermore be added to the aqueous phase.

Suitable interface-active compounds are, in particular, anionic andnonionic surfactants, such as ethoxylates of long-chain alcohols,ethoxylated mono-, di- and trialkylphenols, alkali metal and ammoniumsalts of C₁₂-C₁₈ alkylsulfonic acids or arylsulfonic acids.

For carrying out the polymerisation according to the invention, theorganic phase, also known as the oil phase, is suspended in the aqueousphase. After initiation and performance of the polymerisation, thepolymer can typically be filtered off or removed from the reactionmixture in another manner. Residues of solvents or other additives canbe removed by washing with suitable solvents or, for example, steamdistillation.

In an embodiment, the oil phase comprises inert solvents (porogens) inorder to set the desired pore sizes, in addition to the monomers.

Suitable organic solvents (porogens) are, for example, aliphatichydrocarbons (C₆-C₁₈), such as, for example, hexane, dodecane or benzinemixtures, cycloaliphatic compounds, such as cyclohexane, aromatichydrocarbons, such as toluene, ethylbenzenes or xylenes, or alcohols,such as aliphatic C₄-C₁₂-alcohols, for example heptanol, dodecanol,cyclohexanol, polyethylene glycols or polypropylene glycols of variousmolecular weight, or esters of aliphatic carboxylic acids, such as butylacetate or propyl propionate, or esters of aromatic carboxylic acids,such as propyl benzoate, or esters, such as butyl glycol acetate orglycerol triacetate, or ethers, such as di-n-butyl ether, di-n-amylether, diphenyl ether, ethylene glycol monophenyl ether and ethyleneglycol diethyl ether.

These solvents can be employed individually or as a mixture of two ormore solvents. They can either act as swelling agent or precipitant forthe polymers and in this way influence the porosity.

Examples of swelling agents for the polymers according to the inventionare lower alcohols, aliphatic esters or aromatic hydrocarbons, such astoluene. Examples of precipitants are aliphatic hydrocarbons, such asdodecane or benzine mixtures. The porosity of the polymers can be fixedthrough the type and amount of the solvents in combination with thedegree of cross-linking of the polymer.

Furthermore, one or more initiators acting as free radicals aretypically added to the organic phase.

Examples of free-radical initiators are organic peroxides, such asdi-tertbutyl peroxide, dibenzoyl peroxide, bis(o-methylbenzoyl)peroxide, tert-butyl hydroperoxide, cumene hydroperoxide, diisopropylperoxide dicarbonate, cyclohexanone peroxide, or aliphatic azocompounds, such as α,α′-azobis-isobutyronitrile, azobiscyanovalericacid, 1,1′-azocyclohexane-1,1′-dicarbonitrile or azodicarboxamide.Preference is given to α,α′-azobisisobutyronitrile.

Initiators which can be activated by means of radiation, for example UVradiation, can also be employed in accordance with the invention asfree-radical initiators.

The phase ratios in the suspension polymerisation can typically bevaried in the volume ratio between 1:20 (oil phase to aqueous phase) and2:1, ratios between 1:5 and 1:1, particularly preferably between 1:3 and1:1, are preferred.

The ratio of organic solvent to monomer is typically between 1:20 and4:1, preferably between 1:5 and 3:1, particularly preferably between 1:1and 2.5:1.

The concentration of the initiator, based on the amount of monomer, istypically between 0.01% (by weight) and 10% (by weight), preferablybetween 0.1 and 7% (by weight) and particularly preferably between 0.2and 7% (by weight).

The concentration of stabilisers, based on the amount of suspensionmedium, generally water, is between 0.01 and 7% (by weight), typicallybetween 0.02 and 5% (by weight), particularly preferably between 0.05and 2.5% (by weight).

The suspension polymerisation is then carried out by mixing the twophases with vigorous stirring. In addition, the temperature of themixture is typically kept at 20 to 100° C., preferably 40 to 100° C.,for a period of 1 to 20 hours. The mixture is typically heated at 40 to100° C. over a period of 0.5 to 5 hours and subsequentlypost-polymerised again for several hours at 70 to 100° C. The mixtureshould be stirred throughout the time. These temperature data relate toa system in which water is used as suspension medium. On use of otherpolar solvents instead of water, other temperature ranges may bepossible or appropriate, depending on the boiling point of the solvent.

It is generally advantageous to carry out the polymerisation accordingto the invention in a protective-gas atmosphere.

Finally, the mixture is generally cooled to room temperature, theorganic solvents are removed, if they were added during thepolymerisation, and the product is stored in water, an aqueous buffer ora mixture of water with an organic solvent, such as ethanol.

If necessary, the polymer can be brought to the desired particle-sizedistribution by sieving or another type of classification.

If an inverse suspension polymerisation or an emulsion polymerisation isto be carried out instead of the normal-phase suspension polymerisation,it is known to the person skilled in the art how to modify thecomposition of the reaction solutions.

The polymerisation according to the invention can likewise be carriedout continuously. The particle production here is particularlypreferably carried out using static mixers, in particular micromixers orcaterpillar mixers. In these mixers, the spatial distribution of twocomponents to be mixed is influenced, with utilisation of the flowenergy, by the flow management, for example by separation andrecombination, twisting, distortion and expansion, so that largeinterfaces are formed for diffusive exchange between the components anda particularly uniform particle-size distribution can be achieved due tothe high shear forces. Different mixers and their structure are known.For example, systems of this type are described in EP 1177243.

In order to carry out the reactions, the aqueous phase flows, forexample, continuously with a defined volume flow through the micromixer.The oil phase is subsequently fed in via the second inlet, likewise witha defined, precisely set volume flow. The ratio of the two volume flowscan be in a broad range and depends on the desired particle size, thenature and distribution of the particle sizes, the viscosity of theaqueous and the oil phase, depending on the reaction temperature, andthe reaction kinetics and the requisite ratio of the porogens in the endmixture in order to achieve a suitable pore structure. The volume flowratio between the aqueous phase and the oil phase is preferably 1:10 to100:1, in particular 2:1 to 20:1. The suspension exiting from the staticmixer is preferably polymerised in a continuously operating reactor.

It is likewise possible to reverse the procedure described above. Forexample, for the polymerisation of particularly hydrophilic monomers,the latter are supplied via the aqueous phase. Further details on thesynthesis of bead polymers with the aid of micromixers are given in EP1177243.

It is furthermore known to the person skilled in the art how theparticle size of the resultant polymer can be influenced, inter aliathrough the nature and amount of the addition of suspension stabilisersand interface-active compounds and the stirring intensity. In general,particle diameters between 3 μm and 500 μm, preferably between 3 μm and300 μm, can be produced by means of suspension polymerisation, dependingon the type of stirrer and the rotational speed. The particles can havean irregular shape or can preferably be spherical.

If the polymers according to the invention are prepared by means ofemulsion polymerisation, particle diameters, for example, between 20 nmand 3000 nm, preferably between 100 and 500 nm, can be produced.

The polymers according to the invention can furthermore be prepared orexist in the form of membranes, fibres, hollow fibres, a coating or as amonolithic moulding. Monolithic mouldings are three-dimensional bodies,for example in cylindrical form.

The polymers according to the invention can equally be employed ascomposite materials, i.e., for example, as a coating, for example ofinorganic particles, or a moulding, or mixed with, for example,inorganic constituents. An example thereof are particles of the polymeraccording to the invention which can themselves be magnetised bycopolymerisation of magnetisable particles or of a magnetisable core.

The polymers according to the invention are preferably in the form ofnonporous or particularly preferably porous particles. Depending on thetype and amount of the porogenic solvent employed, the pore sizes cantypically be between 2 and 300 nm. In accordance with the invention,pore size denotes pore radius. Preference is given to pore sizes or poreradii between 2 and 200 nm. In particular, if the polymers according tothe invention are in the form of monolithic mouldings, they can alsohave pore sizes up to 1000 nm.

The pore distribution in the materials according to the invention can bemonomodal, bimodal or oligomodal, preferably monomodal or bimodal.

The pore sizes are preferably measured by means of size exclusionchromatography (SEC). A measurement example in this respect is given inExample 3 and FIG. 2.

The hydrophilic, crosslinked polymers according to the invention areparticularly suitable as sorbents in chromatography, as supportmaterials for the immobilisation of biologically and/or catalyticallyactive substances or as support materials for solid-phase syntheses of,for example, biopolymers, such as nucleic acids or peptides, or forcombinatorial chemistry.

The materials according to the invention are distinguished by goodstability to hydrolysis, in particular in basic medium, and by goodpressure/flow stability. Furthermore, their high hydrophilicity makesthem particularly suitable for biochromatographic methods. The examplescontain additional experimental data on these properties.

The polymers according to the invention are particularly suitable assorbents. For this purpose, they are introduced in a known manner intochromatography columns or capillaries. The polymer according to theinvention can equally be packed in cartridges for chromatographic orother purposes. The present invention therefore also relates tochromatography columns, capillaries or cartridges which contain apolymer according to the invention as sorbent or support material.

The polymers according to the invention can be employed in their nativeform, i.e. without further derivatisation steps, for example, dependingon the porosity set, for size exclusion chromatography (SEC) or forreduction of the salt content of solutions if these solutions containtarget molecules whose molecular weight differs significantly from themolecular weight of the salt,

or provided with other or additional functionalities by one or morederivatisation steps. In particular, they can be derivatised by means ofseparation effectors. These separation effectors may be either ionic orneutral or have a preferred affinity or selectivity for one or moretarget molecules.

The covalent bonding of the separation effectors generally takes placevia the functional groups present on the polymer, such as, for example,hydroxyl groups, for example with formation of an ester or preferably anether function, directly or via a linker or spacer. In another preferredembodiment, the linking to the base material takes place via graftpolymerisation, such as, for example, a cerium(IV)-catalysed graftpolymerisation with formation of a C—C link to the base material.

Separation effectors are known to the person skilled in the art in thearea of chromatography. Separation effectors are substituents which canbe introduced into the support material as early as during the synthesisof the base material or subsequently and influence the surfaceproperties of the support material. In particular, targetedderivatisation of support materials by means of separation effectorsproduces support materials having certain chromatographic properties. Inparticular, separation effectors can have the following terminal groups:

-   a) an ionic or ionisable group, for example    —NR⁷R⁸ or —N⁺R⁷R⁸R⁹,-   in which-   R⁷ and R⁸, independently of one another,    -   H, alkyl having 1-5 C atoms-   and-   R⁹ alkyl having 1-5 C atoms-   with the proviso that, if X=—N⁺R⁷R⁸R⁹, R⁷ and R⁸ cannot be H,    -   guanidinium    -   SO₃ ⁻    -   carboxylic acids-   b) a hydrophobic group, for example —OR¹⁰ or —NHR¹⁰, where R¹⁰    denote C₁-C₂₀-alkyl, C₆-C₂₅-aryl, C₇-C₂₅-alkylaryl or    C₇-C₂₅-arylalkyl, and where these radicals may also have been    derivatised by means of nitrile or C₁-C₅-alkoxy, and where, in    addition, one or more non-adjacent CH₂ groups may have been replaced    by NH or O or, in addition, one or more CH groups may have been    replaced by N;-   c) a metal chelate group;-   d) a thiophilic radical;-   e) a chiral radical.-   f) biomolecules, such as proteins (for example antibodies, protein    A), peptides, amino acids, nucleic acids, saccharides, biotin, etc.-   g) organic radicals which have increased affinity or selectivity for    certain tar-get molecules (for example mono- or bistriazine-based    separation effectors in accordance with WO 9710887 and WO    04/052870).

Thiophilic radicals are disclosed, for example, in EP 0 165 912.

If it is intended firstly to provide the polymer with a universallinker, it can, for example for the introduction of epoxide groups, bereacted with glycidyl compounds, such as butanediol diglycidyl ether.

Furthermore, the polymer according to the invention can, as basematerial, be provided by graft polymerisation with tentacle-likestructures, which can in turn carry the corresponding separationeffectors or be functionalised by means of the latter. The grafting ispreferably carried out in accordance with EP 0 337 144. The chainproduced is linked to the base material via a monomer unit. To this end,the base material according to the invention is suspended in a solutionof monomers, preferably in an aqueous solution. The grafting-on of thepolymeric material is effected in the course of a conventional redoxpolymerisation with exclusion of oxygen. The polymerisation catalystemployed is cerium(IV) ions, since this catalyst forms free-radicalsites on the surface of the base material, from which the graftpolymerisation of the monomers is initiated.

The polymerisation is terminated by termination reactions involving thecerium salts. For this reason, the (average) chain length can beinfluenced by the concentration ratios of the base material, theinitiator and the monomers. Furthermore, uniform monomers or alsomixtures of different monomers can be employed; in the latter case,grafted copolymers are formed.

Suitable monomers for the preparation of the graft polymers are monomersconforming to formula V or VI.

These monomers are (meth) acrylic acid (Y═—COOH), (meth)acrylic acidderivatives where

allylamines (Y═—CH₂ NH₂, —CH₂NR¹²R¹³), (meth)acrylonitriles (Y═—CN),acroleins (Y═—CHO), vinylcarboxylates (Y═—OCOCHR¹⁵R¹⁶) orvinylene-carbonates of the formula VI.

All these monomers are polymerisable substances containing reversiblybonding groups which can be polymerised by means of free radicals inaqueous solution and which may be neutral, acidic or basic.

If the monomers employed are vinylenecarbonates of the formula VI orvinylcarboxylates CR*R**═CR¹¹—OCOCHR¹⁵R¹⁶ of the formula V, the productobtained is preferably subsequently converted into a separating materialcontaining hydroxyl groups. This conversion into a hydroxyl phase isachieved by a mild alkaline or acidic saponification known per se. Forexample, the reaction can be carried out using methanolic K₂CO₃ solutionat room temperature, described, for example, by Y. Tezuka et al., inMacromol. Chem. 186, 685-694 (1985).

In the formulae V and VI, R¹¹ preferably denotes H, i.e. the acrylicacid derivatives are preferred.

Y in formula V preferably denotes

—COCHR¹⁵R¹⁶ or —CH₂NH₂, secondarily preferably—CN or —CHO.

R¹⁵ and R¹⁶, independently of one another, denote H or an alkyl grouphaving up to 5 C atoms. At least one of the radicals R¹⁵ and R¹⁶ ispreferably H. The following radicals are particularly preferred:acetoxy, propionyloxy, butyryloxy, valeryloxy and hexanoyloxy radical.

Z in formula V denotes —OR¹⁴, —OH or —NR¹²R¹³, preferably —NR¹²R¹³.

Preference is given here to compounds in which Z denotes —NR¹²R¹³ andone of the radicals R¹² and R¹³ is H.

The radicals R¹² and/or R¹³ preferably denote an alkyl, phenyl,phenylalkyl or alkylphenyl group, where the alkyl and/or phenyl groupmay be mono- or polysubstituted, preferably mono- or disubstituted,particularly preferably monosubstituted, by an alkoxy, cyano, amino,mono- or dialkylamino, trialkylammonium, carboxyl, sulfonyl, acetoxy oracetamino radical.

The radicals R¹² and/or R¹³ preferably denote alkyl, alkoxyalkyl,cyanoalkyl, aminoalkyl, mono- or dialkylaminoalkyl,trialkylammoniumalkyl, carboxyalkyl or sulfonylalkyl having up to 10 Catoms, preferably up to 6 C atoms, particularly preferably up to 4 Catoms in the alkyl group, which may be linear or branched. R¹² and/orR¹³ accordingly preferably denote methyl, ethyl, propyl, butyl, pentyl,hexyl, methoxymethyl, ethoxymethyl, 2-methoxyethyl, 2-, 3- or4-oxapentyl, 2-, 3-, 4- or 5-oxahexyl, 2-, 3-, 4-, 5- or 6-oxaheptyl,isopropyl, 2-butyl, isobutyl, 2-methylbutyl, isopentyl, 2-methylpentyl,3-methylpentyl, 2-oxa-3-methylbutyl, 3-oxa-4-methylbutyl,2-methyl-3-oxapentyl, 2-methyl-3-oxahexyl, furthermore also heptyl,octyl, nonyl or decyl. Preference is furthermore also given to alkylgroups which are substituted by a cyano, carboxyl or sulfonyl group.Accordingly, R¹² and/or R¹³ preferably denote cyanomethyl, cyanoethyl,cyanopropyl, cyanobutyl, cyanopentyl, cyanohexyl, 2-cyanopropyl,2-cyanobutyl, carboxylmethyl, carboxylethyl, carboxylpropyl,carboxylisopropyl, carboxylbutyl, carboxylpentyl, carboxylhexyl,carboxyl-2-methylpropyl, carboxyl-2-methylbutyl, sulfonylmethyl,sulfonylethyl, sulfonylpropyl, sulfonylbutyl, sulfonylpentyl,sulfonylhexyl, sulfonyl-2-methylpropyl, sulfonyl-2-methylbutyl,sulfonyl-3-methylbutyl, sulfonyl-2-methylpentyl, sulfonyl-3-methylhexylor sulfonyl-2-ethylpentyl. The alkyl groups are furthermore preferablymonosubstituted by an amino, mono- or dialkylamino or trialkylammoniumgroup. The alkyl groups here may be identical or different and have upto 10, preferably up to 6 C atoms, particularly preferably up to 4 Catoms, and accordingly preferably denote dimethylaminoethyl,diethylaminoethyl, methylaminoethyl, methylaminopropyl,dimethylaminopropyl, ethylaminoethyl, propylaminoethyl,propylaminopropyl, dipropylaminoethyl, dipropylaminobutyl,diethylaminoethyl, trimethylammoniumethyl, trimethylammoniumpropyl,trimethylammoniumbutyl, triethylammoniumethyl, triethylammoniumpropyl,triethylammoniumethyl, aminoethyl, aminopropyl, aminobutyl oraminopentyl. All these alkyl and substituted alkyl groups are likewisepreferred as substituents on the phenyl group.

Preference is also given for R¹² and/or R¹³ to a sulfone sulfide of thestructure —(CH₂)_(n)—SO₂—(CH₂)—S— (CH₂)_(n)OH where n=2, 3, 4, 5 or 6,preferably 2, 3 or 4.

R¹² and/or R¹³ preferably also has the meaning of a phenyl group, whichis preferably monosubstituted by cyano, cyanoalkyl, amino, aminoalkyl,mono- or dialkylamino, alkyl, alkoxy, alkoxyalkyl, mono- ordialkylaminoalkyl, trialkylammonium or trialkylammoniumalkyl, carboxyl,carboxyalkyl, sulfonyl or sulfonylalkyl. The preferred meanings of thesesubstituents correspond to the preferred alkyl groups and substitutedalkyl groups indicated above. The substituent on the phenyl group ispreferably in the p-position. p-Acetoxyphenyl, p-aminophenyl orp-acetaminophenyl are likewise preferred meanings for R¹² and/or R¹³.

Preference is furthermore given for R¹² and/or R¹³ to an alkylphenyl orphenylalkyl group, where the preferred meanings indicated for the alkyl,substituted alkyl or substituted phenyl groups shall likewise apply.

Accordingly, the following substituted phenyl groups, for example, areregarded as particularly preferred: 4-cyanophenyl, 4-alkylphenyl,4-(N,N-dimethylamino)phenyl, 4-(N,N-dialkylaminoethyl)phenyl,4-ethoxyphenyl, 4-ethoxyethylphenyl, 4-trialkylammoniumphenyl,4-carboxylphenyl, 4-sulfonylphenyl, phenylethyl, 4-(N-ethylamino)phenylpropyl or 4-cyanophenylethyl.

Furthermore, preferred monomers of the formula V are those in which R¹²and/or R¹³ denote a cyclic or bicyclic radical, which may be aromatic orsaturated, having 5-10 C atoms in which one or more CH or CH₂ groupshave been replaced by N or NH, N or NH and S, or N or NH and O.

R¹² and/or R¹³ accordingly preferably also denote a pyridine radical,imidazolyl radical, indolyl radical, furthermore preferably a pyrrole,pyrimidine, pyrazine, quinoline or isoquinoline radical.

R¹² and/or R¹³ may also, for example, denote a thiazole, thiadiazole,morpholine, triazine, piperazine, benzothiazole, purine, pyrazole,triazole, pyrrolidine or isoxazole radical.

Particular preference is given here to the aromatic, heterocyclicradicals.

The radicals R¹² and R¹³ must, in order to obtain suitable exchangers,be matched to one another in such a way that either both radicalscontain an acidic or basic group or alternatively one of the radicals isneutral. The person skilled in the art is presented with no difficultyin assigning the groups correspondingly and thus assembling suitableradicals for R¹² and R¹³, depending on the function and task of thedesired ion exchanger.

One of the two radicals R¹² and R¹³ is preferably a neutral radical.

R¹⁴ preferably denotes alkyl, alkoxyalkyl, cyanoalkyl, carboxyalkyl orsulfonylalkyl having up to 10 C atoms, preferably having up to 6 Catoms, particularly preferably having up to 4 C atoms, in the alkylgroup, which may be linear or branched. R¹⁴ accordingly preferablydenotes methyl, ethyl, propyl, butyl, pentyl, hexyl, methoxymethyl,ethoxymethyl, 2-methoxyethyl, 2-, 3- or 4-oxapentyl, isopropyl, 2-butyl,isobutyl, 2-methylbutyl, isopentyl, 2-methylpentyl, 3-methylpentyl,2-oxa-3-methylbutyl, 3-oxa-4-methylbutyl, 2-methyl-3-oxapentyl or2-methyl-3-oxahexyl.

Preference is furthermore also given to alkyl groups which aresubstituted by a cyano, carboxyl or sulfonyl group. Accordingly, R¹⁴preferably denotes cyanomethyl, cyanoethyl, cyanopropyl, cyanobutyl,cyanopentyl, cyanohexyl, 2-cyanopropyl, 2-cyanobutyl, carboxylmethyl,carboxylethyl, carboxylpropyl, carboxylisopropyl, carboxylbutyl,carboxylpentyl, carboxylhexyl, carboxyl-2-methylpropyl,carboxyl-2-methylbutyl, sulfonylmethyl, sulfonylethyl, sulfonylpropyl,sulfonylbutyl, sulfonylpentyl, sulfonylhexyl, sulfonyl-2-methylpropyl,sulfonyl-2-methylbutyl, sulfonyl-3-methylbutyl, sulfonyl-2-methylpentyl,sulfonyl-3-methylhexyl or sulfonyl-2-ethylpentyl. All these alkyl andsubstituted alkyl groups are likewise preferred as substituents on thephenyl group.

R¹⁴ preferably also has the meaning of a phenyl group, which ispreferably monosubstituted by cyano, cyanoalkyl, alkyl, alkoxy,alkoxyalkyl, carboxyl, carboxyalkyl, sulfonyl or sulfonylalkyl. Thepreferred meanings of these substituents correspond to the preferredalkyl groups and substituted alkyl groups indicated above. Thesubstituent on the phenyl group is preferably in the p-position.

R* and R** in the monomers of the formula V preferably denote H.

R* and R¹¹ in formula VI preferably denote H.

Chains having between 2 and 100, preferably 5 and 60, in particularbetween 10 and 30, monomer units are typically grafted onto the basematerial.

As already mentioned above, there are sorbents in which exclusively onetype of separation effector is present in the base matrix (“single mode”sorbents), and copolymers or “mixed mode” sorbents in which at least twodifferent types of separation effectors are present in the sorbent.“Single mode” sorbents separate the dissolved substances (solutes) onthe basis of one type of interaction between separation effector andsolutes. On use of mixed mode sorbents, the separation of the dissolvedsubstances (solutes) is based on different types of interactions betweenseparation effector and solutes. Chromatographic methods of this typeare known as mixed mode chromatography.

In the simplest case, for example, the hydrophobicity of the base matrixis utilised in order to provide a sorbent which is suitable for mixedmode chromatography by introduction of an ionic separation effector.Mixed mode sorbents are also accessible by reaction of a base matrixwith two different reactants, one of which introduces, for example, ahydrophobic group, the other an ionic group into the base matrix. Thedisadvantage of the two procedures consists in that the stericrelationship between the different types of separation effectors are notdefined.

This disadvantage is avoided in the case of mixed mode sorbents in whichthe different separation effectors are combined in a ligand. This ligandis bonded to the base matrix.

Both types of mixed mode sorbents mentioned above are described in areview article by L. W. McLaughlin (1989) in Chem. Rev. 89, 309-319. Amixed mode sorbent whose different separation effectors are bonded in asingle ligand can be prepared, for example, from achloropropyl-substituted support material by conversion of the chlorinederivatives into bromine derivatives followed by reaction withbenzyldimethylamine: the ligand is bonded to the base matrix via a C3chain. This is followed by a dimethyl-substituted ammonium group, towhich a lipophilic benzyl radical is bonded. A reverse arrangement ofhydrophobic and ionic separation effectors in a ligand is obtainable byreaction of aminopropyl-substituted support material withp-diethylaminobenzoic acid: in this ligand, the tertiary amino group isoriented distally of the base matrix, while in the former variant, thehydrophobic benzyl group is arranged distally.

Further embodiments of such ligands having two separation effectors aredisclosed in the following documents: WO 96/09116, WO 97/29825, WO00/69872 and WO01/38228. The patent application EP 04028798.9 disclosesmore complex ligands having more than one separation effector each, andanion exchange groups whose nitrogen is in the form of an aza derivativeof polycyclic structures, for example the quininuclidine system.Examples thereof are:

The possible applications of native polymers or polymers according tothe invention provided with separation effectors may include, forexample,

-   -   selective, partially selective or nonselective binding or        adsorption of one or more target components with the aim of        removal from a matrix    -   selective, partially selective or nonselective binding or        adsorption of one or more secondary components with the aim of        removal of the secondary component from a matrix    -   separation of a substance mixture without binding or adsorption        of one or more components merely on the basis of the molecular        size by size exclusion chromatography    -   isolation, enrichment and/or depletion of biopolymers from        natural sources    -   isolation, enrichment and/or depletion of biopolymers from        recombinant sources    -   isolation, enrichment and/or depletion of biopolymers from        immortalised cell lines and culture supernatants thereof or from        plants, in particular transgenic plants    -   isolation, enrichment and/or depletion of biopolymers from        B-cell lines and derivatives thereof, lymph cells and hybridoma        cell lines and culture supernatants thereof    -   isolation, enrichment and/or depletion of proteins and peptides    -   isolation, enrichment and/or depletion of enzymes    -   isolation, enrichment and/or depletion of monoclonal and        polyclonal antibodies and naturally occurring or recombinant        antibody fragments    -   isolation, enrichment and/or depletion of phosphorylated        peptides/proteins and nucleic acids    -   isolation, enrichment and/or depletion of food additives    -   isolation, enrichment and/or depletion of mono- and        polysaccharides    -   isolation, enrichment and/or depletion of glycosylated proteins    -   isolation, enrichment and/or depletion of single-stranded or        double-stranded DNA    -   isolation, enrichment and/or depletion of plasmid DNA    -   isolation, enrichment and/or depletion of RNA    -   isolation, enrichment and/or depletion of viruses    -   isolation, enrichment and/or depletion of host cell proteins    -   isolation, enrichment and/or depletion of oligo- and        polynucleotides    -   isolation, enrichment and/or depletion of liposomes    -   isolation, enrichment and/or depletion of products from blood        and milk    -   isolation, enrichment and/or depletion of low-molecular-weight        active pharmaceutical ingredients (APIs)    -   removal of an API from an API drug carrier (for example an        API/liposome adduct or an API/nanoparticle adduct)    -   isolation, enrichment and/or depletion of enantiomers

Depending on the type of separation effectors, the use of the polymersaccording to the invention corresponds by way of example to affinitychromatography, ion exchange chromatography, hydrophobic interactionchromatography, size exclusion chromatography, chiral chromatography ormixed mode chromatography or liquid-liquid partition chromatography

The polymers according to the invention, in their native form orprovided with separation effectors corresponding to the application, canbe used in known chromatographic conceptional methods in which a sorbentis used. These methods can in principle be divided into discontinuousand continuous methods. Examples of discontinuous methods are mentionedin “Preparative Chromatography” (Ed. H. Schmidt-Traub, Wiley-VCH VerlagWeinheim, 2005, ISBN 3-527-30643-9, page 183-189). Further examples areflash chromatography, expanded bed chromatography, inter alia.Furthermore, the polymers according to the invention, in their nativeform or provided with separation effectors corresponding to theapplication, can be used in continuous methods, such as, for example,simulated moving bed chromatography. Further examples of continuousmethods are described in “Preparative Chromatography” (Ed. H.Schmidt-Traub, Wiley-VCH Verlag Weinheim, 2005, ISBN 3-527-30643-9, page190-204).

Both the continuous methods and also the discontinuous methods can becarried out, depending on the objective, either isocratically or alsousing the gradient technique. It is known to the person skilled in theart how the sorbent according to the invention, native or provided withseparation effectors, is to be employed for the desired objective in oneof the said methods.

The polymers according to the invention can also be used in thin-layerchromatography.

Even without further comments, it is assumed that a person skilled inthe art will be able to utilise the above description in the broadestscope. The preferred embodiments and examples should therefore merely beregarded as descriptive disclosure which is absolutely not limiting inany way.

The complete disclosure content of all applications, patents andpublications mentioned above and below, in particular the correspondingapplication EP 05 016 846.7, filed on Mar. 8, 2005, is incorporated intothis application by way of reference.

EXAMPLES 1. Preparation of a Copolymer from Butanediol Monovinyl Etherand Divinylethyleneurea

1050 ml of deionised water (DI water) are charged into a double-walledreactor, and 0.32 g of tributyl phosphate, 4.2 g of sodium sulfate, 0.01g of sodium laurylsulfonate and 2.1 g of polyvinyl alcohol as stabiliserare dissolved therein. The organic phase, consisting of 96.25 g ofbutanediol monovinyl ether, 78.45 g of divinylethyleneurea, 175 g ofdodecanol and 4.2 g of α,α′-azobisisobutyronitrile, is added to theaqueous phase with stirring at room temperature after mixing anddissolution of the constituents. The suspension is stirred vigorouslyand subsequently warmed to 70° C. while flushing with nitrogen. Afterabout 2 hours, the polymerisation is continued at 80° C. for 4 hours.After cooling to room temperature, the polymer is filtered off withsuction, the porogen is removed by steam distillation, and the productis stored in 20% ethanolic solution.

130 g of polymer, based on the dry weight, are obtained. The averageparticle size is 80 μm.

Characterisation of the porous structure:

-   Specific surface area (BET): 322 m²/g-   The swollen volume of the reaction product is 4.3 ml/g.

2. Determination of the Retention Behaviour of Proteins (NonspecificBinding)

The determination of the retention behaviour of proteins as a functionof the salt concentration is employed to investigate the protein-bindingbehaviour of the unmodified support material. Since proteins only bindnonspecifically to the unmodified support material, it is advantageousif as little background binding as possible occurs.

The binding behaviour of the material according to the invention(prepared corresponding to Example 1) is depicted in comparison with theunmodified copolymer comprising 1,2,-dihydroxy-3-allylaxypropane andmethylenebis-acrylamide, commercially available under the nameFractoPrep® (Merck KGaA, Germany). FIG. 1 shows the binding behaviour ofthe proteins lysozyme and bovine serum albumin and of NaNO₃. Theabbreviation FP stands for FractoPrep®, B/D stands for the copolymeraccording to the invention comprising butanediol monovinyl ether anddivinylethyleneurea. The recovery of the measured proteins, quoted asthe quotient of the photo-metrically determined amount of protein elutedfrom the column under the run conditions to the protein applied to thecolumn, is greater than 90% under all experimental conditions.

3. Size Exclusion Chromatography on the Polymer According to theInvention

An illustrative pore structure of the polymer according to the inventionis shown by way of example in FIG. 2 through the experimentallydetermined distribution coefficient Kd of dextrans of various molecularweights, expressed by the viscosity radius of the dextrans.

4. Base Stability Investigations

The material according to the invention prepared corresponding toExample 1 is stored at room temperature in 0.5 M NaOH (volume ratioNaOH:polymer gel=4:1).

After certain times, the separation behaviour of the polymer is testedwith reference to the retention behaviour in the separation of variouspullulanes (PSS, Mainz, Germany) as marker compounds.

-   Eluent: 100 mM NaCl, 20 mM NaH₂PO₄, pH 7.2-   Column: 300×10 mm, flow rate: 0.8 ml/min, refractive index detector.

FIG. 3 shows the results. It is clearly evident that storage in dilutesodium hydroxide solution has absolutely no effect on the distributioncoefficient.

5.) Separation of a Protein Mixture

The polymer according to the invention, consisting in this example of acopolymer of 65% by weight of butanediol monovinyl ether and 35% byweight of divinylethyleneurea in the form of spherical porous particleshaving an average particle diameter of 107 μm, is provided with cationicseparation effectors by means of Ce(IV)-initiated graft polymerisationof 2-acrylamido-2-methyl-1-propanesulfonic acid corresponding to theprocedure described on page 10 under Preparation Example A2 in WO03/031062. The density of functional SO₃ groups in this polymer isobtained as 1195 μmol, based on 1 g of dry matter. The ion exchangermaterial prepared (BATCH: BDM SO3 DZ38) is introduced into aSuperformance™ glass column, Goetec Labortechnik (depth of the sorbentbed 40 mm, diameter 10 mm) and equilibrated with a buffer consisting of20 mM NaH₂PO₄, pH 6.0. 500 μl of a solution of 5 mg/ml ofchymotrypsinogen A, 5 mg/ml of lysozyme and 5 mg/ml of cytochrome C in20 mM NaH₂PO₄ are applied to the column. After the application, elutionis carried out via a linear gradient over the course of 12 columnvolumes to 100% of a solution of 20 mM NaH₂PO₄, 1 M NaCl, pH 6.0. Theelution behaviour of the polymer according to the invention results inseparation of the individual proteins of the mixture. FIG. 4 shows theassociated chromatogram.

6.) Pressure/Flow Behaviour

The polymer according to the invention in its native form, consisting of65% by weight of butanediol monovinyl ether and 35% by weight ofdivinylethyleneurea (BATCH: BDM PS02/E), is introduced into aSuperformance™ glass column, Goetec Labortechnik, having a diameter of50 mm. The depth of the sorbent bed is 20 cm. The average particlediameter of the spherical porous polymer is 107 μm. The pressure dropover this column is measured as a function of the flow rate of asolution of 100 mM NaCl, 20 mM NaH₂PO₄, pH 6.0. Even at a very high flowrate of 1400 cm/h, the pressure drop is less than 3 bar. FIG. 5 showsthe associated graphical representation of the pressure/flowmeasurement.

1. A polymer based on a copolymer at least comprising a) at least onehydrophilically substituted alkyl vinyl ether of formula I

where R1, R2, R3, independently of one another, is H or C1 to C6 alkyl,and R4 is a radical which carries at least one hydroxyl group, and b) atleast one crosslinking agent of formula II and/or III and/or IV

where X is a divalent alkyl radical having 2 to 5 C atoms in which oneor more methylene groups which are not adjacent and are not located inthe direct vicinity of N may be replaced by O, C═O, S, S═O, SO₂, NH, NOHor N and one or more H atoms of the methylene groups may be substituted,independently of one another, by hydroxyl, C1-C6-alkyl, halogen, NH₂,C5-C10-aryl, NH—(C1-C8)-alkyl, N—(C1-C8)-alkyl₂, C1-C6-alkoxy orC1-C6-alkyl-OH,

where Y1 and Y2 in formula III and IV  are, independently of oneanother, C1 to C10 alkyl or cycloalkyl, where one or more non-adjacentmethylene groups or methylene groups which are not located in the directvicinity of N may be replaced by O, C═O, S, S═O, SO₂, NH, NOH or N andone or more H atoms of the methylene groups may be substituted,independently of one another, by hydroxyl, C1-C6-alkyl, halogen, NH₂,C5-C10-aryl, NH(C1-C8)alkyl, N(C1-C8)alkyl₂, C1-C6-alkoxy orC1-C6-alkyl-OH, or  C6 to C18 aryl, where one or more H atoms in thearyl system may be substituted, independently of one another, byhydroxyl, C1-C6-alkyl, halogen, NH₂, NH(C1-C8)alkyl, N(C1-C8)alkyl₂,C1-C6-alkoxy or C1-C6-alkyl-OH, and A is a divalent alkyl radical having2 to 5 C atoms in which one or more non-adjacent methylene groups ormethylene groups which are not located in the direct vicinity of N maybe replaced by O, C═O, S, S═O, SO₂, NH, NOH or N and one or more H ofthe methylene groups may be substituted, independently of one another,by hydroxyl groups, C1-C6-alkyl, halogen, NH₂, C5-C10-aryl,NH(C1-C8)alkyl, N(C1-C8)alkyl₂, C1-C6-alkoxy or C1-C6-alkyl-OH, whichpolymer has been derivatised by separation effectors, or has beenderivatised by structures which have been attached to the polymer bygraft polymerisation, or has been derivatised by structures which havebeen attached to the polymer by graft polymerisation with cerium(IV)catalysis.
 2. A polymer according to claim 1, wherein R4 in formula I isa straight-chain or branched C1 to C10 alkyl radical, in which one ormore non-adjacent methylene groups may be replaced by O, C═O, S, S═O,SO₂, NH, NOH, or N and/or in which one or more H atoms may besubstituted, independently of one another, by C1-C6-alkyl, C5-C10-aryl,halogen, NH₂, NH(C1-C8)alkyl, N(C1-C8)alkyl₂, C1-C6-alkoxy orC1-C6-alkyl-OH and in which at least one OH group is present either onthe C1 to C10 alkyl radical or on a substituent, or a cycloaliphaticradical, , in which one or more non-adjacent methylene groups may bereplaced by O, C═O, S, S═O, SO₂, NH, NOH, or N and/or in which one ormore H atoms of the cycloaliphatic radical may be substituted,independently of one another, by C1-C6-alkyl, C5-C10-aryl, halogen, NH₂,NH(C1-C8)alkyl, N(C1-C8)alkyl₂, C1-C6-alkoxy or C1-C6-alkyl-OH, where atleast one OH group is present either on the cycloaliphatic ring or on aside chain or substituent, or a C6 to C18 aryl radical, where one ormore H atoms in the aryl radical may be substituted, independently ofone another, by hydroxyl, C1-C6-alkyl, C5-C10-aryl, halogen, NH₂,NH(C1-C8)alkyl, N(C1-C8)alkyl₂, C1-C6-alkoxy or C1-C6-alkyl-OH, where atleast one OH group is present either on the aryl radical or on a sidechain or substituent, or a C5 to C18 heteroaryl radical, where one ormore H atoms in the heteroaryl radical may be substituted, independentlyof one another, by hydroxyl, C1-C6-alkyl, C5-C10-aryl, halogen, NH₂,NH(C1-C8)alkyl, N(C1-C8)-alkyl₂, C1-C6-alkoxy or C1-C6-alkyl-OH, whereat least one OH group is present either on the heteroaryl radical or ona side chain or substituent.
 3. A polymer according to claim 1, whereinthe hydrophilically substituted alkyl vinyl ether is a compound offormula I in which R4 is a radical which carries a hydroxyl group.
 4. Apolymer according to claim 1, wherein the hydrophilically substitutedalkyl vinyl ether is 1,2-ethanediol monovinyl ether, 1,3-propanediolmonovinyl ether, 1,4-butanediol monovinyl ether, 1,5-pentanediolmonovinyl ether, 1,6-hexanediol monovinyl ether, diethylene glycolmonovinyl ether or cyclohexanedimethanol monovinyl ether.
 5. A polymeraccording to claim 1, wherein the crosslinking agent isdivinylethyleneurea (1,3-divinylimidazolin-2-one) ordivinylpropyleneurea (1,3-divinyltetrahydropyrimidin-2-one).
 6. Apolymer according to claim 1, which is porous having pore sizes between2 and 200 nm.
 7. A polymer according to claim 1, which is in the form ofparticles having a diameter between 3 and 300 μm.
 8. A polymer accordingto claim 1, which has been derivatised by separation effectors.
 9. Apolymer according to claim 1, which has been derivatised by structureswhich have been attached to the polymer by graft polymerisation.
 10. Apolymer according to claim 1, which has been derivatised by structureswhich have been attached to the polymer by graft polymerisation withcerium(IV) catalysis.
 11. A polymer according to claim 9, wherein thestructures are copolymers which have been produced from two or moredifferent monomers.
 12. A process for preparing a polymer, comprisingcopolymerizing, with addition of one or more porogens, at least onehydrophilically substituted alkyl vinyl ether of the formula I and atleast one crosslinking agent of formula II and/or III and/or IV

where R1, R2, R3, independently of one another, are H or C1 to C6 alkyl,and R4 is a radical which carries at least one hydroxyl group, and

where X is a divalent alkyl radical having 2 to 5 C atoms in which oneor more methylene groups which are not adjacent and are not located inthe direct vicinity of N may be replaced by O, C═O, S, S═O, SO₂, NH, NOHor N and one or more H atoms of the methylene groups may be substituted,independently of one another, by hydroxyl, C1-C6-alkyl, halogen, NH₂,C5-C10-aryl, NH—(C1-C8)-alkyl, N—(C1-C8)-alkyl₂, C1-C6-alkoxy orC1-C6-alkyl-OH,

where Y1 and Y2 in formula III and IV  are, independently of oneanother, C1 to C10 alkyl or cycloalkyl, where one or more non-adjacentmethylene groups or methylene groups which are not located in the directvicinity of N may be replaced by O, C═O, S, S═O, SO₂, NH, NOH or N andone or more H of the methylene groups may be substituted, independentlyof one another, by hydroxyl, C1-C6-alkyl, halogen, NH₂, C5-C10-aryl,NH(C1-C8)alkyl, N(C1-C8)alkyl₂, C1-C6-alkoxy or C1-C6-alkyl-OH, or  C6to C18 aryl, where one or more H in the aryl system may be substituted,independently of one another, by hydroxyl, C1-C6-alkyl, halogen, NH₂,NH(C1-C8)alkyl, N(C1-C8)alkyl₂, C1-C6-alkoxy or C1-C6-alkyl-OH, and A isa divalent alkyl radical having 2 to 5 C atoms in which one or morenon-adjacent methylene groups or methylene groups which are not locatedin the direct vicinity of N may be replaced by O, C═O, S, S═O, SO₂, NH,NOH or N and one or more H of the methylene groups may be substituted,independently of one another, by hydroxyl, C1-C6-alkyl, halogen, NH₂,C5-C10-aryl, NH(C1-C8)alkyl, N(C1-C8)alkyl₂, C1-C6-alkoxy orC1-C6-alkyl-OH.
 13. A process according to claim 12, wherein in thecompound of formula I, R4 is a straight-chain or branched C1 to C10alkyl radical, in which one or more non-adjacent methylene groups may bereplaced by O, C═O, S, S═O, SO₂, NH, NOH, or N and/or in which one ormore H atoms may be substituted, independently of one another, byC1-C6-alkyl, C5-C10-aryl, halogen, NH₂, NH(C1-C8)alkyl, N(C1-C8)alkyl₂,C1-C6-alkoxy or C1-C6-alkyl-OH and in which at least one OH group ispresent either on the C1 to C10 alkyl radical or on a substituent, or acycloaliphatic radical, in which one or more non-adjacent methylenegroups may be replaced by O, C═O, S, S═O, SO₂, NH, NOH, or N and/or inwhich one or more H atoms of the cycloaliphatic radical may besubstituted, independently of one another, by C1-C6-alkyl, C5-C10-aryl,halogen, NH₂, NH(C1-C8)alkyl, N(C1-C8)alkyl₂, C1-C6-alkoxy orC1-C6-alkyl-OH, where at least one OH group is present either on thecycloaliphatic ring or on a side chain or substituent, or a C6 to C18aryl radical, where one or more H atoms in the aryl radical may besubstituted, independently of one another, by hydroxyl, C1-C6-alkyl,C5-C10-aryl, halogen, NH₂, NH(C1-C8)alkyl, N(C1-C8)alkyl₂, C1-C6-alkoxyor C1-C6-alkyl-OH, where at least one OH group is present either on thearyl radical or on a side chain or substituent, or a C5 to C18heteroaryl radical, where one or more H atoms in the heteroaryl radicalmay be substituted, independently of one another, by hydroxyl,C1-C6-alkyl, C5-C10-aryl, halogen, NH₂, NH(C1-C8)alkyl, N(C1-C8)alkyl₂,C1-C6-alkoxy or C1-C6-alkyl-OH, where at least one OH group is presenteither on the heteroaryl radical or on a side chain or substituent. 14.A process according to claim 12, wherein a free-radical suspensionpolymerisation is carried out.
 15. A process according to claim 12,wherein a free-radical suspension polymerisation is carried out in wateras suspension medium in the presence of at least one suspensionstabiliser and one or more optional further additives, inorganic saltsor interface-active compounds.
 16. A process according to claim 12,wherein the temperature during the polymerisation is between 40 and 100°C.
 17. A process according to claim 12, wherein hydrophilicallysubstituted alkyl vinyl ethers and crosslinking agents are in a weightratio between 10:90 and 80:20.
 18. A chromatography column, capillary orcartridge containing, as sorbent or support material, a polymer based ona copolymer at least comprising a) at least one hydrophilicallysubstituted alkyl vinyl ether of formula I

where R1, R2, R3, independently of one another, is H or C1 to C6 alkyl,and R4 is a radical which carries at least one hydroxyl group, and b) atleast one crosslinking agent of formula II and/or III and/or IV

where X is a divalent alkyl radical having 2 to 5 C atoms in which oneor more methylene groups which are not adjacent and are not located inthe direct vicinity of N may be replaced by O, C═O, S, S═O, SO₂, NH, NOHor N and one or more H atoms of the methylene groups may be substituted,independently of one another, by hydroxyl, C1-C6-alkyl, halogen, NH₂,C5-C10-aryl, NH—(C1-C8)-alkyl, N—(C1-C8)-alkyl₂, C1-C6-alkoxy orC1-C6-alkyl-OH,

where Y1 and Y2 in formula III and IV  are, independently of oneanother, C1 to C10 alkyl or cycloalkyl, where one or more non-adjacentmethylene groups or methylene groups which are not located in the directvicinity of N may be replaced by O, C═O, S, S═O, SO₂, NH, NOH or N andone or more H atoms of the methylene groups may be substituted,independently of one another, by hydroxyl, C1-C6-alkyl, halogen, NH₂,C5-C10-aryl, NH(C1-C8)alkyl, N(C1-C8)alkyl₂, C1-C6-alkoxy orC1-C6-alkyl-OH, or  C6 to C18 aryl, where one or more H atoms in thearyl system may be substituted, independently of one another, byhydroxyl, C1-C6-alkyl, halogen, NH₂, NH(C1-C8)alkyl, N(C1-C8)alkyl₂,C1-C6-alkoxy or C1-C6-alkyl-OH, and A is a divalent alkyl radical having2 to 5 C atoms in which one or more non-adjacent methylene groups ormethylene groups which are not located in the direct vicinity of N maybe replaced b O, C═O, S, S═O, SO₂, NH, NOH or N and one or more H of themethylene groups may be substituted, independently of one another, byhydroxyl groups, C1-C6-alkyl, halogen, NH₂, C5-C10-aryl, NH(C1-C8)alkyl,N(C1-C8)alkyl₂, C1-C6-alkoxy or C1-C6-alkyl-OH.
 19. A method ofproviding a sorbent in chromatography, support material for theimmobilisation of biologically or catalytically active substances orsupport material for a solid-phase synthesis, comprising providing asthe sorbent or support material a polymer based on a copolymer at leastcomprising a) at least one hydrophilically substituted alkyl vinyl etherof formula I

where R1, R2, R3, independently of one another, is H or C1 to C6 alkyl,and R4 is a radical which carries at least one hydroxyl group, and b) atleast one crosslinking agent of formula II and/or III and/or IV

where X is a divalent alkyl radical having 2 to 5 C atoms in which oneor more methylene groups which are not adjacent and are not located inthe direct vicinity of N may be replaced by O, C═O, S, S═O, SO₂, NH, NOHor N and one or more H atoms of the methylene groups may be substituted,independently of one another, by hydroxyl, C1-C6-alkyl, halogen, NH₂,C5-C10-aryl, NH—(C1-C8)-alkyl, N—(C1-C8)-alkyl₂, C1-C6-alkoxy orC1-C6-alkyl-OH,

where Y1 and Y2 in formula III and IV  are, independently of oneanother, C1 to C10 alkyl or cycloalkyl, where one or more non-adjacentmethylene groups or methylene groups which are not located in the directvicinity of N may be replaced by O, C═O, S, S═O, SO₂, NH, NOH or N andone or more H atoms of the methylene groups may be substituted,independently of one another, by hydroxyl, C1-C6-alkyl, halogen, NH₂,C5-C10-aryl, NH(C1-C8)alkyl, N(C1-C8)alkyl₂, C1-C6-alkoxy orC1-C6-alkyl-OH, or  C6 to C18 aryl, where one or more H atoms in thearyl system may be substituted, independently of one another, byhydroxyl, C1-C6-alkyl, halogen, NH₂, NH(C1-C8)alkyl, N(C1-C8)alkyl₂,C1-C6-alkoxy or C1-C6-alkyl-OH, and A is a divalent alkyl radical having2 to 5 C atoms in which one or more non-adjacent methylene groups ormethylene groups which are not located in the direct vicinity of N maybe replaced by O, C═O, S, S═O, SO₂, NH, NOH or N and one or more H ofthe methylene groups may be substituted, independently of one another,by hydroxyl groups, C1-C6)alkyl, halogen, NH₂, C5-C10-aryl,NH(C1-C8)alkyl, N(C1-C8)alkyl₂, C1-C6-alkoxy or C1-C6-alkyl-OH.
 20. Achromatography column, capillary or cartridge according to claim 18,wherein R4 in formula I is a straight-chain or branched C1 to C10 alkylradical, in which one or more non-adjacent methylene groups may bereplaced by O, C═O, S, S═O, SO₂, NH, NOH, or N and/or in which one ormore H atoms may be substituted, independently of one another, byC1-C6-alkyl, C5-C10-aryl, halogen, NH₂, NH(C1-C8)alkyl, N(C1-C8)alkyl₂,C1-C6-alkoxy or C1-C6-alkyl-OH and in which at least one OH group ispresent either on the C1 to C10 alkyl radical or on a substituent, or acycloaliphatic radical, in which one or more non-adjacent methylenegroups may be replaced by O, C═O, S, S═O, SO₂, NH, NOH, or N and/or inwhich one or more H atoms of the cycloaliphatic radical may besubstituted, independently of one another, by C1-C6-alkyl, C5-C10-aryl,halogen, NH₂, NH(C1-C8)alkyl, N(C1-C8)alkyl₂, C1-C6-alkoxy orC1-C6-alkyl-OH, where at least one OH group is present either on thecycloaliphatic ring or on a side chain or substituent, or a C6 to C18aryl radical, where one or more H atoms in the aryl radical may besubstituted, independently of one another, by hydroxyl, C1-C6-alkyl,C5-C10-aryl, halogen, NH₂, NH(C1-C8)alkyl, N(C1-C8)alkyl₂, C1-C6-alkoxyor C1-C6-alkyl-OH, where at least one OH group is present either on thearyl radical or on a side chain or substituent, or a C5 to C18heteroaryl radical, where one or more H atoms in the heteroaryl radicalmay be substituted, independently of one another, by hydroxyl,C1-C6-alkyl, C5-C10-aryl, halogen, NH₂, NH(C1-C8)alkyl, N(C1-C8)alkyl₂,C1-C6-alkoxy or C1-C6-alkyl-OH, where at least one OH group is presenteither on the heteroaryl radical or on a side chain or substituent. 21.A chromatography column, capillary or cartridge according to claim 18,wherein the hydrophilically substituted alkyl vinyl ether is a compoundof formula I in which R4 is a radical which carries a hydroxyl group.22. A chromatography column, capillary or cartridge according to claim18, wherein the hydrophilically substituted alkyl vinyl ether is1,2-ethanediol monovinyl ether, 1,3-propanediol monovinyl ether,1,4-butanediol monovinyl ether, 1,5-pentanediol monovinyl ether,1,6-hexanediol monovinyl ether, diethylene glycol monovinyl ether orcyclohexanedimethanol monovinyl ether.
 23. A chromatography column,capillary or cartridge according to claim 18, wherein the crosslinkingagent is divinylethyleneurea (1,3-divinylimidazolin-2-one) ordivinylpropyleneurea (1,3-divinyltetrahydropyrimidin-2-one).
 24. Achromatography column, capillary or cartridge according to claim 18,wherein the polymer is porous having pore sizes between 2 and 200 nm.25. A chromatography column, capillary or cartridge according to claim18, wherein the polymer is in the form of particles having a diameterbetween 3 and 300 μm.
 26. A chromatography column, capillary orcartridge according to claim 18, wherein the hydrophilically substitutedalkyl vinyl ether is 1,2-ethanediol monovinyl ether, 1,3-propanediolmonovinyl ether, 1,4-butanediol monovinyl ether, 1,5-pentanediolmonovinyl ether, 1,6-hexanediol monovinyl ether, diethylene glycolmonovinyl ether or cyclohexanedimethanol monovinyl ether, and the thecrosslinking agent is divinylethyleneurea (1,3-divinylimidazolin-2-one)or divinylpropyleneurea (1,3-divinyltetrahydropyrimidin-2-one).
 27. Apolymer according to claim 1, wherein the hydrophilically substitutedalkyl vinyl ether is 1,2-ethanediol monovinyl ether, 1,3-propanediolmonovinyl ether, 1,4-butanediol monovinyl ether, 1,5-pentanediolmonovinyl ether, 1,6-hexanediol monovinyl ether, diethylene glycolmonovinyl ether or cyclohexanedimethanol monovinyl ether, and the thecrosslinking agent is divinylethyleneurea (1,3-divinylimidazolin-2-one)or divinylpropyleneurea (1,3-divinyltetrahydropyrimidin-2-one).
 28. Achromatography column, capillary or cartridge containing, as sorbent orsupport material, a polymer according to claim
 1. 29. A method ofproviding a sorbent in chromatography, support material for theimmobilisation of biologically or catalytically active substances orsupport material for a solid-phase synthesis, comprising providing asthe sorbent or support material a polymer according to claim
 1. 30. Apolymer according to claim 1, wherein R4 in formula I is astraight-chain or branched C1 to C10 alkyl radical, in which one or morenon-adjacent methylene groups may be replaced by O, C═O, S, S═O, SO₂,NH, NOH, or N and/or in which one or more H atoms may be substituted,independently of one another, by C1-C6-alkyl, C5-C10-aryl, halogen, NH₂,NH(C1-C8)alkyl, N(C1-C8)alkyl₂, C1-C6-alkoxy or C1-C6-alkyl-OH and inwhich at least one OH group is present either on the C1 to C10 alkylradical or on a substituent, or a cycloaliphatic radical having 5 to 10C atoms, in which one or more non-adjacent methylene groups may bereplaced by O, C═O, S, S═O, SO₂, NH, NOH, or N and/or in which one ormore H atoms of the cycloaliphatic radical may be substituted,independently of one another, by C1-C6-alkyl, C5-C10-aryl, halogen, NH₂,NH(C1-C8)alkyl, N(C1-C8)alkyl₂, C1-C6-alkoxy or C1-C6-alkyl-OH, where atleast one OH group is present either on the cycloaliphatic ring or on aside chain or substituent, or a C6 to C18 aryl radical, where one ormore H atoms in the aryl radical may be substituted, independently ofone another, by hydroxyl, C1-C6-alkyl, C5-C10-aryl, halogen, NH₂,NH(C1-C8)alkyl, N(C1-C8)alkyl₂, C1-C6-alkoxy or C1-C6-alkyl-OH, where atleast one OH group is present either on the aryl radical or on a sidechain or substituent, or a C5 to C18 heteroaryl radical, where one ormore H atoms in the heteroaryl radical may be substituted, independentlyof one another, by hydroxyl, C1-C6-alkyl, C5-C10-aryl, halogen, NH₂,NH(C1-C8)alkyl, N(C1-C8)alkyl₂, C1-C6-alkoxy or C1-C6-alkyl-OH, where atleast one OH group is present either on the heteroaryl radical or on aside chain or substituent.